Interpretation of Opiate Urine Drug Screens

Interpretation of Opiate Urine Drug Screens
Urine drug testing is highly reliable, but false positives can rarely occur for some drugs.
As always, clinical judgment is necessary when interpreting test results.
The length of time a drug can be detected in the urine varies due to several factors,
including hydration, dosing, metabolism, body mass, urine pH, duration of use, and a
drug’s particular pharmacokinetics. (See table below for some “average” times for
different drugs.)
Length of Time Drugs of Abuse Can Be
Detected in UrineDrug
Short-acting (eg, pentobarbital)
Long-acting (eg, phenobarbitol)
Short-acting (eg, lorazepam)
Long-acting (eg, diazepam)
Cocaine metabolites
Single use
Moderate use (4 times/wk)
Daily use
Long-term heavy smoker
Heroin (detected as morphine)
7-12 h
48 h
48 h
24 h
3 wk
30 d
2-4 d
5-7 d
10-15 d
30 d
48 h
48 h
2-4 d
48-72 h
2-4 d
6-48 h
-- Mayo Clinic Proc. 2008; 83(1)66-76
Sometimes the specific drug ingested is not detected, but instead one of its metabolites
is found.
Opiate/Opioid Metabolism
Two types of urine drug tests are used for HealthPartners patients – immunoassay and
gas chromatography-mass spectrometry (GC/MS).
The first test done is the immunoassay. This can be susceptible to false positives, so
when a positive result is obtained it is confirmed by GC/MS.or the pain management
urine drug screen,/MS is done for these drugs regardless of the immunoassay screen
result: morphine, codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone.
The GC/MS confirmation assays are highly reliable and specific tests with very rare
Fentanyl (Duragesic) is not easily detected in either urine or serum. Our current system
does not allow accurate determination of the presence of this drug. HealthPartners
may purchase new equipment that will make this possible within the next year. Until
that happens, you will not be able to tell whether a patient is using fentanyl (Duragesic
patches) based on the results of the urine drug screen.
Current urine drug testing methods were designed to identify illicit use of drugs in the forensic
or occupational setting. In this setting, high specificity was needed to avoid a false positive
result and this was carried out by using a relatively high cutoff concentration needed to trigger
a positive result. In the setting of pain management compliance testing, both drug
pharmacokinetics (how the body acts on a drug) and testing limitations that affect the results of
urine testing must be understood for proper interpretation.
Although the name “opiate” is often used to describe any member of the class of drugs that
acts on opioid receptors, the term “opiate” properly refers to the natural alkaloids found in
opium poppy resin (Papaver somniferum), which include morphine, codeine and thebaine. The
term “opioid” refers to the synthetic and semi-synthetic opioid receptor drugs, including
heroin, hydromorphone, hydrocodone, oxycodone, oxymorphone, buprenorphine, fentanyl,
and methadone.
1.5 - 6.5
Concentrations above the
cutoff will screen positive
normorphine, hydromorphone (<2.5%)
morphine, hydrocodone (<11%), norcodeine
4 - 12
oxymorphone, noroxycodone
3.5 - 9
hydromorphone, norhydrocodone, dihydrocodeine
* bolded metabolites are identical to pharmaceutically available drugs
Assay Technologies
The pain management urine drug screen offered within the HealthPartners Family of Care
consists of two steps. First, a qualitative (positive/negative) immunoassay screen is completed,
including tests for opiates (300 ng/mL cutoff), oxycodone (100 ng/mL cutoff), amphetamine,
barbiturate, benzodiazepines, cocaine, methadone, PCP, propoxyphene, and THC. These drugs
are reported as positive if they are present at a concentration above the designated cutoff (see
Regions Hospital Laboratory Toxicology website on myPartner for specific cutoffs and drugs
detected) and confirmed as positive by GC/MS. For the pain management panel only,
regardless of the screen results, GC/MS confirmation for the following drugs are completed and
reported individually as positive/negative with a detection limit of 100 ng/mL: morphine,
codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone. This allows for higher
sensitivity and specificity along with offering results for each drug individually.
In general, immunoassay technologies are susceptible to interfering substances (false positives)
and cross-reactivity (true positives for non-target drugs, due to structural similarity) to varying
degrees. Accordingly, each result needs to be interpreted in the context of the clinical picture
and in conjunction with our confirmatory method of gas chromatography/mass spectrometry
(GC/MS). The immunoassay for opiates is primarily targeted to detecting morphine,
hydrocodone, dihydrocodeine, codeine, 6-acetylmorphine (metabolite of heroin), and
hydromorphone. Due to that assay’s insensitivity for oxycodone, the oxycodone assay is utilized
to detect oxycodone and oxymorphone. The GC/MS confirmation assays are highly reliable and
specific tests with very rare interferences.
Detection Windows
The window to detect the presence of a particular drug in a person’s urine is highly dependent
on multiple factors, such as:
Hydration - More dilute urine from high fluid intake may cause dilution of drug and
therefore a negative result due to levels present but below the cutoff. Conversely, a
patient may greatly reduce fluid intake in order to concentrate their urine when
trying to mask inappropriate reduced intake of their prescribed drug.
Dosing - If a patient is on a low dose or has a long interval between doses, the level
of drug in their urine may be too low to be detected by the immunoassay or
confirmation assay, i.e. below the cutoff. Similarly, the time between the last dose of
a drug taken and the collection of the urine specimen may affect if the drug is
present at concentrations adequate to produce a positive result.
Metabolism - Metabolism is unique to each individual, determined by genetic and
environmental factors. Genetic polymorphisms of the CYP450 2D6 enzyme can cause
individuals to be poor or rapid metabolizers of opioids and other drugs metabolized
by those enzymes1. Additionally, environmental influences further complicate
metabolism. For example, co-administered drugs that are also metabolized by
CYP450 enzymes used by the opioids or that inhibit CYP450 2D6 cause decreased
metabolism, see Table below. Conversely, rifampin and dexamethasone are known
to induce CYP450 2D6, causing increased metabolism of opioids with a resulting
shortened detection window. Other factors affecting metabolism include age, sex,
ethnicity, and renal or liver impairment.
Other Factors
The detection window of a drug is also affected by: duration of use, body mass, urine pH and a
drug’s particular chemistry, i.e. half-life and volume of distribution. If a negative result is
obtained for a drug prescribed to the patient, the entire clinical picture must be taken into
consideration to determine if the patient was: 1) not taking the drug, 2) taking a lower dose
than instructed, or 3) taking the drug properly but the results were negative due to one of
above factors. Similarly, if a positive result is obtained for a drug not prescribed to the patient,
the entire clinical picture must be taken into consideration to determine if the patient was
taking the non-prescribed drug, has a false positive result (applies to immunoassay only) or if
the drug is simply a metabolite of a prescribed drug (as applicable).
The following figure exemplifies the amount of variation possible in the concentration of drug
present in individuals taking the same dose of a drug2. In this example, 36 healthy participants
that had taken no drugs in the previous 30 days were given one of 3 doses (n=12 per dose) of
OxyContin®. The following shows the combined distribution of multiple urine specimens taken
from each individual days 3 and 4 after dosing began:
Interpretation Cautions
Interferents, sensitivity and cutoffs vary by immunoassay, see Reference 3 for a review
of immunoassay types and interferents; EMIT assays are used by Regions Hospital’s
Toxicology lab, which serves the entire HP Family of Care.
Hydromorphone has been shown to be a minor metabolite in chronic pain patients
receiving high amounts of morphine.4,5
Hydrocodone has been shown to be a minor metabolite detectable in patients on high
amounts of codeine6; as the metabolite of hydrocodone, hydromorphone may also be
detectable in these cases.
A small amount of codeine may be evident with morphine administration due to
manufacturing impurities (up to 0.04% of parent dose); high amounts of morphine
should be present in these cases.7
A small amount of hydrocodone may be evident with oxycodone administration due to
manufacturing impurities; high amounts of oxycodone should be present in these cases 8
Ingestion of poppy seeds or herbal teas containing Papaveris fructus may cause a true
positive opiate (morphine, codeine) results.9,10
Oxymorphone has a longer half-life than oxycodone; a patient prescribed oxycodone
may only have oxymorphone detected in urine.
Heroin is metabolized to morphine, which may be detectable after its use.
The dose taken cannot be extrapolated from drug screen results, even if a quantitative
result is obtained.
1. Smith HS. Opioid Metabolism. Mayo Clinic Proceedings 2009; 84:613-624.
2. Couto JE, Webster L, et al. Use of an algorithm applied to urine drug screening to assess
adherence to an OxyContin® regimen. Journal of Opioid Management 2009; 5:359-364.
3. Reisfield GM, Salazar E, Bertholf RL. Rational use and interpretation of urine drug testing
in chronic opioid therapy. Annals of Clinical & Laboratory Science 2007; 37:301-314.
4. Wasan AD, Michna E, et al. Interpreting urine drug tests: prevalence of morphine
metabolism to hydromorphone in chronic pain patients treated with morphine. Pain
Medicine 2008; 9:918-923.
5. Cone EJ, Heit HA, et al. Evidence of morphine metabolism to hydromorphone in pain
patients chronically treated with morphine. Journal of Analytical Toxicology 2006; 30:15.
6. Oyler JM, Cone EJ, et al. Identification of hydrocodone in human urine following
controlled codeine administration. Journal of Analytical Toxicology 2000; 24:530-535.
7. West R, Crews B, et al. Anomalous observations of codeine in patients on morphine.
Therapeutic Drug Monitoring 2009; 31:776-778.
8. West R, West C, et al. Anomalous observations of hydrocodone in patients on oxycodone.
Clinica Chimica Acta 2011; 412:29-32.
9. Pelders MG and Ros JJW. Poppy seeds: differences in morphine and codeine content and
variation in inter- and intra-individual excretion. Journal of Forensic Sciences 1996;
10. Meadway C, George S and Braithwaite R. Opiate concentrations following ingestion of
poppy seed products – evidence for ‘the poppy seed defence’. Forensic Science
International 1998; 96:29-38.
11. Moeller K, Lee K, Kissack J. Urine Drug Screening: Practical Guide for Clinicians. Mayo
Clinic Proc. 2008; 83: 66-76.
Questions: Please reply to this e-mail, and your questions(s) will be directed to the author of
this Pearl, Kalen Olson, PhD, Clinical Laboratory Director.
Pearl Archive:
All Pearl recommendations are consistent with professional society guidelines,
and reviewed by HealthPartners Physician Leadership.